Abstract: The formation and maintenance of microbial biofilms is shown to be dependent on signaling pathways mediated by cyclic di-GMP. In the absence of such signaling, microbes detach from a biofilm, and thereby become more readily treatable with conventional antibiotics. Chemical or biological means that interfere with cyclic-di-GMP signaling induce biofilm dissolution, providing for a new class of antibiotics. In one embodiment of the invention, the biofilm inhibitor is an analog of cyclic-di-GMP, which competitively or non-competitively blocks signaling. In another embodiment of the invention, the biofilm inhibitor is a genetic sequence that interferes with cyclic-di-GMP synthesis or signaling.